PROJECT SUMMARY This proposal requests funding for a macromolecular X-ray Diffraction (XRD) system to be placed in the X-ray Crystallography Facility of the Department of Chemistry & Biochemistry at the University of Delaware (UD). We propose to purchase a state-of-the-art macromolecular XtaLAB Synergy-R system from Rigaku Americas Corporation. This instrument will provide much needed core research capabilities that are currently limited due to the age of the existing macromolecular XRD system at UD. At present, the sole macromolecular XRD at UD is a 20-year-old Rigaku RUH3R/R-axis IV, which has surpassed its useful lifetime and is not presently functioning. The only local resource for researchers needing to screen protein crystals and to optimize diffraction conditions is an XRD designed for small molecule crystal structure determination. The proposed instrument will provide a crucial tool to a recent upsurge of NIH funded investigators with a need to solve protein crystal structures. The high X-ray brilliance, high detector sensitivity, and short exposure times offered by the Rigaku XtaLAB Synergy-R will be vastly superior to the aging Rigaku system. To maximize access to and utilization of this critical resource to a wide user base across the University, the XtaLAB Synergy-R XRD, together with its associated cryo system, will be housed and managed in an existing Crystallography Core Facility. A well-defined management plan and high level of institutional commitment will ensure the sustainability of this broadly used instrument. The proposed instrument will provide critical support for the NIH-funded research programs of 9 major and 4 minor users spanning the Departments of Chemistry & Biochemistry; Biological Sciences; Medical and Molecular Sciences; and Chemical and Biomolecular Engineering. The Rigaku XRD will greatly enable advances across a wide range of biomedical research areas, including structural enzymology, microbiology, protein engineering, protein assemblies, signaling and regulatory pathways for enzymes, molecular design, and the development of small molecule probes and therapeutics. The instrument will also provide support to several major NIH initiatives at UD, including the Chemistry-Biology Interface (CBI) Training Program, multiple Centers of Biomedical Research Excellence (COBRE) on Delaware?s campus, the Delaware IDeA Network of Biomedical Research Excellence (INBRE), and the Center for Translational Cancer Research (CTCR).